DESCRIPTION: (Applicant's Abstract) The overall goal of this project is the development of a digital brain image database (BRAID) that integrates image-processing and visualization capabilities, the statistical analysis of spatial and clinical data, and management of digital brain atlases, all accessible from a common user interface. The integration of these components is critical to BRAID's success in deriving clinically meaningful associations between the structure and function of the human brain. We envision BRAID as a platform for the analysis of image-based clinical trials (IBCT's), three of which we are currently analyzing. Our preliminary results demonstrate the need for efficient automated segmentation of image data for large numbers of subjects, for powerful statistical analysis of these data, and for atlases that reflect the pathophysiology being investigated in a given IBCT. In the IBCT's we are analyzing, cortical and white-matter lesions are central to the structure-function hypotheses being addressed. Toward these ends, we propose three specific aims to extend BRAID's functionality: development of statistical algorithms for automated segmentation of brain lesions, development of Bayesian methods for multivariate atlas-based lesion-deficit analysis, augmented atlas that will include certain white-matter structures in addition to cortical and subcortical structures. These extensions build on the strengths of BRAID's morphologically factored image representation developed in the first phase of this grant. We will test these extensions to BRAID by applying our methods to data sets from the Psychopathology of Frontal Lobe Injury in Childhood (FLIC) study, the Baltimore Longitudinal Study on Aging (BLSA), and the Cardiovascular Health Study (CHS). The BLSA and CHS are large-scale epidemiological image-based clinical trials, the former a 9-year longitudinal study with annual MR and neuropsychiatric data on 180 subjects, the latter an NHLBI sponsored project with extensive demographic, functional, and MR data on over 3,600 participants. The FLIC study is collecting brain MR and extensive neuropsychiatric data on 100 children after traumatic brain injury. In analyzing these data, and data from other IBCT's, BRAID will increase our understanding of the functional organization of the human brain.